Association of SNPs in HLA-C and ZNRD1 Genes With HIV-1 Mother-to-Child Transmission in Zambia Population.

Abstract

Human leukocyte antigen C (HLA-C) and Zinc ribbon domain containing 1 (ZNRD1) are considered HIV-1 restriction factors and are expressed in the placenta. Variations in HLA-C and ZNRD1 genes are known to influence HIV-1 infection, including viral replication and progression to AIDS. Little is known about the role of variants in these genes in HIV-1 mother-to-child transmission. We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321, rs3869068) variants in a Zambian population composed of 333 children born to HIV-1+ mothers (248 HIV-1 noninfected/85 HIV-1 infected) and 97 HIV-1+ mothers. Genotypic distribution of HLA-C and ZNRD1 were in Hardy-Weinberg equilibrium, except for HLA-C rs10484554 in both groups. In mothers, no significant differences were observed in their allele and genotypic distributions for both genes. The T and TT variants (rs10484554-HLA-C) were significantly more frequent among HIV-1+ children, specifically those who acquired the infection in utero (IU) and intrapartum (IP). For ZNRD1, the T allele (rs3869068) was more frequent in HIV-1- children, showing significant differences in relation to those infected via IP and postpartum (PP). The CT and TT genotypes were significantly more frequent in HIV-1- children. Variations in HLA-C (T and TT-rs10484554) and ZNRD1 (T and CT/TT-rs3869068) can increase and decrease the susceptibility to HIV-1 infection via mother-to-child transmission, respectively. Further studies are encouraged focusing on a greater number of variants and sample size, with functional validation and in other populations.